Fluid analysis with fluid seal system

ABSTRACT

In one example in accordance with the present disclosure, a fluid analysis system is described. The fluid analysis system includes an inlet channel to an analysis chamber. The analysis chamber is to receive a fluid sample to be analyzed. The fluid analysis system also includes a fluid branch having a fluidic junction along the inlet channel and a gas chamber to house a volume of trapped gas, the gas chamber being in fluid communication with the fluid branch. The fluid analysis system also includes a sealing fluid delivery system to fill the fluid branch with a sealing fluid and a heater adjacent the gas chamber to heat the gas chamber such that the trapped gas expands to push the sealing fluid into the inlet channel to seal the analysis chamber.

BACKGROUND

Microfluidic systems are used to perform different operations on smallvolumes of fluid. For example, microfluidic systems can move, mix,separate, and perform fluid analysis of different types of fluids. Suchsystems can be used in the medical industry, for example to analyze DNA,detect pathogens, perform clinical diagnostic testing, and aiding insynthetic chemistry. Such microfluidic systems may also be used in otherindustries.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate various examples of the principlesdescribed herein and are part of the specification. The illustratedexamples are given merely for illustration, and do not limit the scopeof the claims.

FIG. 1 is a block diagram of a fluid analysis system with a fluid seal,according to an example of the principles described herein.

FIG. 2 is a flowchart of a method for sealing a fluid analysis systemwith a sealing fluid, according to an example of the principlesdescribed herein.

FIGS. 3A-3E depict operation of a fluid analysis system with a fluidseal, according to an example of the principles described herein.

FIGS. 4A and 4B depict operation of a fluid analysis system with a fluidseal, according to an example of the principles described herein.

FIG. 5 is a diagram of a fluid analysis system with a fluid seal,according to an example of the principles described herein.

FIG. 6 is a diagram of a fluid analysis system with a fluid seal,according to an example of the principles described herein.

Throughout the drawings, identical reference numbers designate similar,but not necessarily identical, elements. The figures are not necessarilyto scale, and the size of some parts may be exaggerated to more clearlyillustrate the example shown. Moreover, the drawings provide examplesand/or implementations consistent with the description; however, thedescription is not limited to the examples and/or implementationsprovided in the drawings.

DETAILED DESCRIPTION

Cellular biology is a field of biology that studies the structure,function, and operation of cells. In an example, a biological sample maycontain cells or other biological components of interest that are to beanalyzed. As a particular example, a biological sample may includebacteria that is to be incubated and studied. To study a biologicalsample, the biological sample may be introduced into an analysis volumeand observed with data being collected as the biological sample isobserved. In some examples external stimulus such as heat may be appliedto the biological sample. A greater understanding of the cells or otherbiological component of interest may lead to scientific developments.

While such biological analysis may yield beneficial results, someenvironmental conditions of these analyses may skew results. Forexample, such microfluidic systems may be susceptible to unwantedevaporation. That is, the small reaction volumes and largesurface-to-volume ratios in microfluidic systems may mean thatmicrofluidic experiments are sensitive to loss of fluid on a level thatotherwise may be considered insignificant in macroscopic experiments.Take a bacterial incubation as an example. In such an experiment, acollection of cells or bacteria is mixed with a drug or reagent andincubated on-chip for minutes to hours, often at above-room temperaturessuch as 37° C. For a variety of reasons, the reaction chamber may beconnected to outside atmosphere and other air volumes by vents, ports,inlet channels, and outlet channels. Evaporation from open surfaces mayreduce the test volume, change concentrations of reagents, and affectthe incubation in other ways. Each of these factors may impact bacterialgrowth.

As another example, unwanted evaporation during high-temperature holdsof nucleic acid amplification reactions, either PCR or isothermal, mayimpact the amplification of DNA or RNA. As described above, in PCR, afluid sample is thermally cycled up to temperatures as high as 100° C.This high temperature may induce intensive evaporation from any opensurface connected to the reaction volume. Such evaporation results in aloss of the fluid sample, introduction of air bubbles, which may pulsatewith temperature and move the fluid in undesired manners, and may resultin accumulation of fluorescent die, which may skew any test results.

Accordingly, the present specification describes a system that isolatesthe analysis chamber from vent ports and other open surfaces once theanalysis chamber is filled and a biological reaction is started.Specifically, the present specification discloses a method of isolatingwater-based test fluids by immiscible oils.

That is, to reduce evaporation, a fluid sample should be isolated fromthe rest of the system during device operation. Accordingly, the presentfluid analysis system blocks pathways between the fluid sample andexternal and internal volumes, including inlet and outlet channelsleading to the analysis chamber. Specifically, the present fluidanalysis system accomplishes the task by introducing an auxiliaryservice fluid, an “oil,” with low saturated vapor pressure. After theanalysis chamber is filled with the fluid sample, oil is pushed to fillsegments of the inlet and outlet channels. Doing so isolates the fluidsample from vent ports and other free surfaces and reduces or eliminatesevaporation. The oil is transported into the sealing position byelevating the device operating temperature which increases the volume ofa trapped gas bubble. Expanding gas pushes the oil into its designatedlocations.

Specifically, the present specification describes a fluid analysissystem. The fluid analysis system includes an inlet channel to ananalysis chamber. The analysis chamber is to receive a fluid sample tobe analyzed. The fluid analysis system also includes a fluid branchhaving a fluidic junction along the inlet channel. A gas chamber influid communication with the fluid branch houses a volume of trappedgas. The fluid analysis system also includes a sealing fluid deliverysystem to fill the fluid branch with a sealing fluid. A heater of thefluid analysis system is adjacent the gas chamber to heat the gaschamber such that the trapped gas expands to push the sealing fluid intothe inlet channel to seal the analysis chamber.

In an example, a first capillary break at the fluidic junction preventsthe sealing fluid from entering the inlet channel prior to heating thegas chamber. A second capillary break in the fluid branch upstream ofthe gas chamber may prevent backflow of the sealing fluid through thefluid branch. In this example, the second capillary break has a smalleropening than the first capillary break. In an example, the capillarybreak has different characteristics as compared to the first capillarybreak. For example, the length, width, capillary break gap, holdingpressure, and/or hydrophobicity of the second capillary break may bedifferent than those of the first capillary break. The fluid analysissystem may further include a gas chamber capillary break to prevent thesealing fluid from entering the gas chamber.

In an example, the sealing fluid has a lower vapor pressure than thefluid sample and is immiscible with the fluid sample. A number ofactuators may transport the sealing fluid and the fluid samplethroughout the fluid analysis system.

The present specification also describes a method. According to themethod, a sealing fluid is introduced through a fluid branch to afluidic junction with an inlet channel of an analysis chamber. A fluidsample is introduced into the analysis chamber via the inlet channel.Trapped gas in a gas chamber that is in fluid communication with thefluid branch is heated. Via expansion of the trapped gas in the gaschamber, the sealing fluid is transported into a body of the inletchannel to seal the analysis chamber and prevent evaporation from theanalysis chamber.

In an example, the sealing fluid is at least one of silicon oil, mineraloil, hexadecane, a hydrofluoroether-based fluid, and afluorocarbon-based fluid. In an example, the sealing fluid is preventedfrom entering the body of the inlet channel until the gas chamber isheated. The sealing fluid is also prevented from flowing into the gaschamber and backflowing through the fluid branch.

In another example, a fluid analysis system includes an analysis chamberhaving an inlet channel and an outlet channel, a first fluid branchhaving a fluidic junction along the inlet channel, and a second fluidbranch having a fluidic junction along the outlet channel. A first gaschamber is in fluid communication with the first fluid branch and asecond gas chamber is in fluid communication with the second fluidbranch. The fluid analysis system includes a sealing fluid deliverysystem to fill the first fluid branch and second fluid branch with asealing fluid. The fluid analysis system also includes a heating systemto heat the first gas chamber and the second gas chamber such thattrapped gas expands to push the sealing fluid into the inlet channel andoutlet channel.

In an example, the first gas chamber and the first fluid branch havedifferent properties than the second gas chamber and second fluidbranch, respectively. For example, the first gas chamber may have adifferent size than the second gas chamber. As another example, thefirst fluid branch may have a different length than the second fluidbranch. The sealing fluid delivery system may include a shared sealingreservoir between the first fluid branch and the second fluid branch. Inan example, the heating system includes a first heater adjacent thefirst gas chamber and a second heater adjacent the second gas chamber.

In summary, such a fluid analysis system 1) provides an evaporation freeenvironment in which any number of biological or chemical reactions maytake place, 2) provides a seal using immiscible fluid which does notevaporate and does not interfere with the biological or chemicalreactions; and 3) does not include moveable parts which are susceptibleto mechanical breakdown. However, the devices disclosed herein mayaddress other matters and deficiencies in a number of technical areas.

Further, as used in the present specification and in the appendedclaims, the term “a number of” or similar language is meant to beunderstood broadly as any positive number including 1 to infinity.

Turning now to the figures, FIG. 1 is a block diagram of a fluidanalysis system (100) with a fluid seal, according to an example of theprinciples described herein. As described above, the fluid analysissystem (100) uses a thermo-pneumatic seal that operates on the principlethat trapped gas bubbles change volume with temperature. Specifically,at a first temperature, T1, a gas bubble may be confined within a gaschamber (106). At a second higher temperature, T2, the bubble expandsinto a fluid branch (104) where a sealing fluid is present. Theexpansion of the gas towards the immiscible oil pushes the oil throughthe fluid branch (104) until it enters and seals an inlet channel (102)of an analysis chamber.

In some examples, the fluid analysis system (100) may be a microfluidicstructure. In other words, the inlet channel (102), fluid branch (104),and gas chamber (106) may be microfluidic structures. A microfluidicstructure is a structure of sufficiently small size (e.g., of nanometersized scale, micrometer sized scale, millimeter sized scale, etc.) tofacilitate conveyance of small volumes of fluid (e.g., picoliter scale,nanoliter scale, microliter scale, milliliter scale, etc.).

As described above, the fluid analysis system (100) may be used toanalyze any number of fluids. For example, the fluid analysis system(100) may be implemented in a life science application. As such, thefluid sample analyzed by the fluid analysis system (100) may be of avariety of types and may be used for a variety of applications. Forexample, the fluid may be a biological fluid. Accordingly, thebiological fluid may be introduced into the analysis chamber via theinlet channel (102). Following introduction, the biological fluid may beanalyzed and observed. In some examples, fluid analyzed may be abiological fluid that may include solvent or aqueous-basedpharmaceutical compounds, as well as aqueous-based biomoleculesincluding proteins, enzymes, lipids, antibiotics, mastermix, primer, DNAsamples, cells, or blood components, all with or without additives, suchas surfactants or glycerol.

In an example, the fluid analysis system (100) includes an inlet channel(102) to an analysis chamber. The analysis chamber is to receive a fluidsample that is to be ultimately analyzed. This fluid sample isintroduced into the analysis chamber via the inlet channel (102). Insome examples, the fluid sample described herein may be a biologicalfluid such as those mentioned above. The fluid flow through the inletchannel (102) may be generated by a pump that is disposed upstream ordownstream from the analysis chamber. In some examples, the pump may bean integrated pump, meaning the pump is integrated into a wall of themicrofluidic channel. In some examples, the pump may be an inertial pumpwhich refers to a pump which is in an asymmetric position within themicrofluidic channel. In some examples, the pump may be a thermal inkjetresistor, or a piezo-drive membrane or any other displacement device.

The fluid analysis system also includes a fluid branch (104) that has afluidic junction along the inlet channel (102). That is, the fluidbranch (104) is a conduit through which a sealing fluid may flow. Theremay be a junction between the fluid branch (104) and the inlet channel(102). It is through this fluidic junction that a sealing oil isintroduced into the inlet channel (102) to block environmental exposureof the analysis chamber.

The type of sealing fluid may vary. For example, the sealing fluid maybe in contact with the environment. As such, the sealing fluid may havea low vapor pressure so that it does not evaporate under testconditions. The sealing fluid may also be immiscible with the fluidsample. That is, it may be the case that the sealing fluid is in contactwith the fluid sample as depicted in FIGS. 3A-4B. Accordingly, thesealing fluid may be selected so as to not mix and alter the biologicalor chemical reactions. In a particular example, the sealing fluid may besilicon oil, mineral oil, hexadecane, a hydrofluoroether-based fluid, ora fluorocarbon-based fluid.

The fluid analysis system (100) also includes a gas chamber (106) thatis in fluid communication with the fluid branch (104) and that houses avolume of trapped gas. The gas chamber (106) provides a force thatdrives the sealing fluid into a sealing position. The present gaschamber (106) provides the force without mechanically actuatable parts.That is, other fluid systems may have mechanical parts or otherwiseinvolve moving parts. However, such mechanical systems may not functionproperly in microfluidic devices with small sizes. That is, small movingparts are difficult to fabricate and control. During operation, they mayget stuck due to random mechanical, interfacial, and electrostaticforces and are therefore may be unreliable.

Accordingly, the fluid analysis system (100) of the presentspecification includes a sealing system that has a working principlebased on thermal expansion and contraction of gas bubbles due totemperature changes. That is, as the temperature of the gas in the gaschamber (106) increases, the gas inside expands. This expansion of thegas may be used to move components of the fluid analysis system (100).Specifically, the gas chamber (106) is in fluid communication with afluid branch (104), such that as the gas expands past the confines ofthe gas chamber (106), the gas fills the fluid branch (104). However,the sealing fluid may already be present in the fluid branch (104).Accordingly, the expansion of the trapped gas may move the sealing fluidfrom the fluid branch (104) into the inlet channel (102). In otherwords, the present fluid analysis system (100) uses a static force topush a secondary fluid into an inlet channel (102) to isolate ananalysis chamber.

The gas in the gas chamber (106) may be any type of gas, such as air,sterile air, oxygen, hydrogen, carbon dioxide, inert gas (e.g.,nitrogen, helium, argon, etc.), or a combination thereof. Features ofthe fluid analysis system (100), such as the dimensions of the gaschamber (106), fluid branch (104), inlet channel (102), and associatedcapillary breaks described below, may be based on specific properties ofthe sealing fluid and the gas. For example, gaps of the capillary breaksmay depend on the surface tension of the sealing fluid and its contactangle with the fluid branch (104) walls.

The fluid analysis system (100) also includes a sealing fluid deliverysystem (FIG. 1, 108 ) to fill the fluid branch (104) with a sealingfluid. In the example depicted in FIGS. 3A-3F the sealing fluid deliverysystem (FIG. 1, 108 ) is a reservoir (213) that stores sealing fluidand/or an inlet through which a sealing fluid is introduced into thefluid analysis system. In other examples such as that depicted in FIG. 5, the sealing fluid delivery system (FIG. 1, 108 ) may include an inletport. The sealing fluid flow may be generated by a pump. In someexamples, the pump may be an integrated pump, meaning the pump isintegrated into a wall of a channel of the sealing fluid deliverysystem. In some examples, the pump may be an inertial pump which refersto a pump which is in an asymmetric position within the channel of thesealing fluid delivery system. In some examples, the pump may be athermal inkjet resistor, or a piezo-drive membrane or any otherdisplacement device.

The fluid analysis system (100) also includes a heater (110) that isadjacent the gas chamber (106). As described above, the expansion of thetrapped gas is triggered by a change in temperature. Accordingly, theheater (110) heats the gas chamber (106) such that the trapped gasexpands to push the sealing fluid into the inlet channel (102) to sealthe analysis chamber. The heater (110) may be in any position such asembedded in a substrate underlying the gas chamber (106), within the gaschamber (106), or adjacent the gas chamber (106) on the same substrateas the gas chamber (106).

The heater (110) may take a variety of forms including a thermal inkjetresistors and power field effect transistors. In other examples, theheater (110) may be formed of a resistive material such as indium tinoxide (ITO), tin (IV) oxide (SnO₂), zinc tin oxide (ZTO), polysilicon,tungsten silicon nitride (WSiN), a tantalum-aluminum alloy or aluminumzinc oxide among others. In some examples, the heater (110) may befabricated in the form of a thin film deposited by physical or chemicalvapor deposition, among other manufacturing techniques.

FIG. 2 is a flowchart of a method (200) for sealing a fluid analysissystem (FIG. 1, 100 ) with a sealing fluid, according to an example ofthe principles described herein. According to the method (200), asealing fluid is introduced (block 201) through a fluid branch (FIG. 1,104 ) to a fluidic junction with an inlet channel (FIG. 1, 102 ) of ananalysis chamber. That is, as described above, a fluid sample isintroduced into an analysis chamber via an inlet channel (FIG. 1, 102 ).This inlet channel (FIG. 1, 102 ), if unblocked, may expose the contentsof the analysis chamber to the environment, which may result in unwantedevaporation. A fluidic junction is created between a fluid branch (FIG.1, 104 ) and the inlet channel (FIG. 1, 102 ). Prior to or during fluidsample introduction, the sealing fluid resides in this fluid branch(FIG. 1, 104 ) and may be prevented from entering the inlet channel(FIG. 1, 102 ) via a capillary break.

Accordingly, the fluid sample is introduced (block 202) into theanalysis chamber via the inlet channel (FIG. 1, 102 ). As describedabove, this may be performed via a pump that is disposed in or upstreamof the inlet channel (FIG. 1, 102 ).

Once the fluid sample is within the analysis chamber, trapped gas in agas chamber (FIG. 1, 106 ) that is in fluid communication with the fluidbranch (FIG. 1, 104 ) is heated (block 203). Doing so causes the trappedgas therein to expand. Upon expansion, the trapped gas leaves theconfines of the gas chamber (FIG. 1, 106 ) into the fluid branch (FIG.1, 104 ). However, the sealing fluid is also present in the fluid branch(FIG. 1, 104 ). Accordingly, via expansion of the trapped gas in the gaschamber (FIG. 1, 106 ), the sealing fluid is transported (block 204)from the fluid branch (FIG. 1, 104 ) into a body of the inlet channel(FIG. 1, 102 ). In so doing, the sealing fluid prevents additional fluidand ambient air from entering the analysis chamber. As such, the sealingfluid plug prevents evaporation from the analysis chamber.

As described above, such a method (200) may be used to seal an analysischamber wherein any number of chemical operations are to be performed.In one particular example, the analysis chamber is to house a PCRoperation. In this example, the PCR components, i.e., fluid sample, PCRmastermix, primers, enzymes, etc. are introduced into the analysischamber via the inlet channel (FIG. 1, 102 ). Following introduction,the inlet channel (FIG. 1, 102 ) is sealed as described in the method(200). With the analysis chamber sealed from air vents and ports whichexpose the PCR components to evaporation, PCR may be carried out by, forexample, cyclically heating and cooling the analysis chamber.

While particular reference is made to PCR, the fluid manipulation system(FIG. 1, 100 ) may be used in other molecular diagnostics such asisothermal amplification reactions such as loop-mediated isothermalamplification (LAMP) and recombinase polymerase amplification (RPA).

In another example, a fluid sample including bacteria may be introducedinto the analysis chamber via the inlet channel (FIG. 1, 102 ).Following the method (200) of sealing the analysis chamber, bacterialincubation may occur as intended without being affected by the effectsof evaporation.

FIGS. 3A-3E depict operation of a fluid analysis system (100) with afluid seal, according to an example of the principles described herein.FIGS. 3A-3E clearly depict the fluid analysis system (100) with theinlet channel (102) that leads to the analysis chamber and the fluidbranch (104) through which the sealing fluid is provided. FIGS. 3A-3Ealso depict the gas chamber (106) that is adjacent the fluid branch(104) and the heater (110) which raises the temperature to expand thetrapped gas. Specifically, as depicted in FIGS. 3A-3E, the trapped gasinside the gas chamber (106) expands, upon heating, to push sealingfluid from the fluid branch (104) into the inlet channel (102). In FIGS.3A-4B, the sealing fluid is depicted as angled fill, while the fluidsample is indicated as a grid fill, and the trapped gas is depicted withno fill.

FIGS. 3A-3E depict other components of the fluid analysis system (100).Specifically, the fluid analysis system (100) may include a firstcapillary break (212-1) at the fluidic junction to prevent the sealingfluid from entering the inlet channel (102) prior to heating the gaschamber (106). That is, if left to fluid dynamics, the sealing fluid mayleak into the inlet channel (102) and may therefore be introduced intothe analysis chamber. The first capillary break (212-1) prevents thesealing fluid from entering the body of the inlet channel (102) untilthe gas chamber (106) is heated. That is, the capillary breaks stabilizethe fluid flow during priming and keep it stable against smalltemperature variations during device operation.

In general, as the sealing fluid flows, a meniscus is created at thefirst capillary break (212-1) into the inlet channel (102). Thismeniscus creates pressure due to surface tension that prevents thesealing fluid from further flowing into the inlet channel (102). Thatis, the sloped or tapered walls of the capillary breaks (212) create adecrease in diameter sufficient to stop capillary action. In anotherexample, a capillary break may be defined by a hydrophobic material or anon-porous material (such as glass, plastic, or metal). The holdingpressure of the meniscus is inversely proportion to a width of the gapof the capillary break (212) such that the width of the gap of thecapillary break (212) and the angle of the capillary break (212) wallsdictate the holding pressure.

The fluid analysis system (100) may further include a second capillarybreak (212-2) in the fluid branch upstream of the gas chamber (106).This second capillary branch (212-2) prevents backflow of the sealingfluid through the fluid branch (104). Note that a capillary break (212)may be a fluidic diode in that fluid flow is allowed in a singledirection while prevented in the opposite direction. Accordingly, thetapered walls of the second capillary break (212-2) allow fluid fromflowing in a direction indicated by the arrow. However, fluid flow isprevented in the opposite direction.

The fluid analysis system (100) may further include a gas chambercapillary break (212-3) to prevent the sealing fluid from entering thegas chamber (106). That is, as described above, the surface tension atthe meniscus formed by the gas chamber capillary break (212-3) preventsthe sealing fluid from entering the gas chamber (106). However, flow inthe opposite direction, i.e., of expanded gas out of the gas chamber(106) towards the fluid branch (104) is permitted.

Operation of the fluid analysis system (100) is now presented. Asdepicted in FIG. 3A, the sealing fluid may be introduced into the fluidbranch (104). Specifically, the sealing fluid passes by the secondcapillary break (212-2). However, due to the operation and structure ofthe first capillary break (212-1), the sealing fluid is prevented fromentering the body of the inlet channel (102) until the gas chamber (106)is heated. Similarly, due to the gas chamber (106) not having air vents,the sealing fluid does not flow into the gas chamber (106) and insteadtraps gas in the gas chamber (106). In examples where the fluid analysissystem (100) includes a gas chamber capillary break (212-3), theoperation and structure of the gas chamber capillary break (212-2) maysecondarily aid in the prevention of sealing fluid flow into the gaschamber (106) and may stabilize the sealing fluid interface at apredetermined location. Similarly, due to the operation and structure ofthe second capillary break (212-2), backflow of the sealing fluidthrough the fluid branch (104) is prevented. Prior to activation of theheater (110), the trapped gas is at a first temperature and remains inthe gas chamber (106) and does not interact with the sealing fluid inthe fluid branch (104).

As depicted in FIG. 3B, a fluid sample is introduced to the analysischamber through the inlet channel (102). In FIG. 3C, the heater (110) isactivated, which causes the trapped gas to expand. The gas chambercapillary break (212-3) is such that the trapped gas may expand into thefluid branch (104). The expansion of the trapped gas pushes the sealingfluid. As the temperature is further increased, the trapped gascontinues to expand to push against the sealing fluid. Specifically, aportion of the sealing fluid is pushed backwards to the second capillarybreak (212-2) as while another portion pushes against the firstcapillary break (212-1) as depicted in FIG. 3D.

As depicted in FIG. 3E, the temperature is further increased to continuethe expansion of the trapped gas. The increased force due to theexpansion of the trapped gas may overcome the holding pressure of themeniscus at the first capillary break (212-1), such that the sealingfluid breaks through the first capillary break (212-1) and enters intothe inlet channel (102) to block and seal and isolate the analysischamber.

Note that the increased pressure depicted in FIG. 3E may exceed theholding pressure of the first capillary break (212-1). However, thisincreased pressure may not exceed the holding pressure of the secondcapillary break (212-2). That is, as described above, the holdingpressure of a capillary break (212) is dependent upon the geometric andother characteristics of the capillary break (212). Accordingly, thesecond capillary break (212-2) may have different characteristics ascompared to the first capillary break (212-1). Examples of differentcharacteristics include a length, width, capillary break gap, holdingpressure, and hydrophobicity. For example, as a specific example, thesecond capillary break (212-2) may have a smaller capillary break gapand a higher holding pressure and hydrophobicity. In a more particularexample, the length of the second capillary break (212-2) may be shorterand the width of the second capillary break (212-2) may be narrower. Asa specific example, the second capillary break (212-2) may have asmaller opening than the first capillary break (212-1). As such, thesecond capillary break (212-2) may have a greater holding pressure thanthe first capillary break (212-1). Doing so ensures that the trapped gasdoes not expand upward and away from the inlet channel (102), but ratherdirects the entire force of gas expansion towards the inlet channel(102). That is, the second capillary break (212-2) may be formed so asto have a higher holding pressure than the first capillary break(212-1). As another example, the hydrophobicity, i.e., contact anglebetween the fluid and the walls may be different with a larger contactangle resulting in a larger holding pressure. In this example, thesecond capillary break (212-2) may have a larger contact angle betweenthe fluid and the walls as compared to the contact angle of the firstcapillary break (212-1). As a result of the operation of the fluidmanipulation system (100), the sealing fluid fills a section of theinlet channel (102), which isolates the analysis chamber from theeffects of evaporation inducing environmental conditions.

FIGS. 4A and 4B depict operation of a fluid analysis system (100) with afluid seal, according to an example of the principles described herein.In the example depicted in FIGS. 4A and 4B, the analysis chamber (416)has both an inlet channel (102) and an outlet channel (414). That is, afluid sample may be introduced into the analysis chamber (416) via theinlet channel (102). As described above, the fluid sample may includePCR fluids, bacterial incubation samples, or other biological fluids.After a reaction or operation is performed, the fluid may be evacuatedfrom the analysis chamber (416) via the outlet channel (414).

FIGS. 4A and 4B also depict various vents (418) that may be found alongthe fluidic path. For simplicity, a single vent (418) is depicted with areference number. As described above, evaporation through these vents(418) may change the chemical composition of the analysis chamber (416)which may have an impact on the processes carried out within theanalysis chamber (416) and/or skew the results of the analysis of theprocesses carried out. As there may be vents (418) along both the inletchannel (102) and the outlet channel (414), the fluid analysis system(100) of the present specification may include fluid sealing systems forboth the inlet channel (102) and the outlet channel (414). FIG. 4Adepicts the fluid analysis system (100) following introduction of afluid sample (in grid lines) but prior to activation of the fluidsealing system to push sealing fluid (angled lines) into a sealingposition.

As such, the fluid analysis system (100) includes a first fluid branch(104-1) that may have a fluidic junction along the inlet channel (102)while a second fluid branch (104-2) may have a fluidic junction alongthe outlet channel (414). The fluid analysis system (100) also includesa first gas chamber (106-1) in fluid communication with the first fluidbranch (104-1) and a second gas chamber (106-2) in fluid communicationwith the second fluid branch (104-2). The fluid analysis system (100)also includes a sealing fluid delivery system (FIG. 1, 106 ) to fill thefirst fluid branch (104-1) and the second fluid branch (104-2) with asealing fluid. In an example and as depicted in FIGS. 4A and 4B, thesealing fluid delivery system (FIG. 1, 106 ) may include a sharedsealing source between the first fluid branch (104-1) and the secondfluid branch (104-2). That is, a single fluidic inlet (420) may supplysealing fluid to both fluid branches (104). In other examples, eachfluid branch (104) may receive sealing fluid from an independent sealingreservoir.

In an example, the fluid analysis system (100) includes a heating systemto heat the first gas chamber (106-1) and the second gas chamber (106-2)such that trapped gas expands to push the sealing fluid into the inletchannel (102) and the outlet channel (414). In an example, the heatingsystem may include a single heater that heats both the first gas chamber(106-1) and the second gas chamber (106-2). However, in an example, theheating system includes a first heater (110-1) adjacent the first gaschamber (106-1) and a second heater (110-2) adjacent the second gaschamber (106-2). In so doing, each of the gas chambers (106) may beindividually actuated.

That is, it may be that a user desires to first seal an inlet channel(102) and then seal an outlet channel (414). In this example, a user mayfirst activate a first heater (110-1) to cause trapped air in the firstgas chamber (106-1) to expand and seal the inlet channel (102). At somesubsequent point in time, the second heater (110-2) may be activated tocause trapped air in the second gas chamber (106-2) to expand and sealthe outlet channel (414). As such, the present fluid analysis system(100) provides flexibility and customization in execution of theoperations of the microfluidic analysis device. Accordingly, the fluidanalysis system (100) may include, or be coupled to, a controller thatoperates the heaters (110) and any associated pumps to move fluidthroughout the system and to trigger expansion of the gas in the gaschambers (106).

In addition to the different heaters (110-1, 110-2), the sequentialsealing of the inlet channel (102) and the outlet channel (414) mayoccur by having characteristics of components associated with the inletchannel (102) and outlet channel (414) being different. For example, thefirst gas chamber (106-1) and the first fluid branch (104-1) may havedifferent properties, i.e., volumes, widths, surface properties, thenthe second gas chamber (106-2) and second fluid branch (104-2),respectively.

As described above, the capillary breaks (212) may be different as well.For example, a first capillary break (212-1) associated with the inletchannel (102) may have a different width than the first capillary break(212-4) associated with the outlet channel (414) and the secondcapillary break (212-2) associated with the first fluid branch (104-1)may have a different width than the second capillary break (212-5)associated with the second fluid branch (104-2). As another example, thefirst capillary break (212-4) associated with the outlet channel (414)may be more hydrophobic than the first capillary break (212-1)associated with the inlet channel (102). As such, there may be a varietyof structural features that may be customized to ensure sealing asintended for a particular application.

The operation of these capillary breaks (212-1, 212-2, 212-3, 212-4,212-5, 212-6) may be performed as described above.

As described above, FIG. 4B depicts the fluid analysis system (100)after the sealing fluid has been introduced into the body of the inletchannel (102) and outlet channel (414). This sealing process may beperformed as depicted in FIGS. 3A-3E. As clearly depicted in FIG. 4B,the vents (418), which in FIG. 4A were in fluid communication with thefluid sample, are now blocked by the sealing fluid. As such, there areno vents (418), ports, or other components of the analysis chamber (416)that expose the fluid sample therein to the environment. Thus, thepresent system prevents unwanted evaporation that may occur when thefluid sample may be exposed to the environment.

FIG. 5 is a diagram of a fluid analysis system (100) with a fluid seal,according to an example of the principles described herein. FIG. 5clearly depicts the first and second gas chambers (106-1, 106-2) as wellas the fluid branches (104-1, 104-2) coupled thereto. FIG. 5 alsodepicts the inlet channel (102) and outlet channel (414) of the analysischamber (416) as described above as well as various capillary breaks(212). Note that in the example depicted in FIG. 5 , the fluid analysissystem (100) does not include the gas chamber capillary breaks. In thisexample, sealing fluid is prevented from entering the gas chambers(106-1, 106-2) due to their being a lack of a vent in the gas chambers(106). In the example depicted in FIG. 5 , the fluid analysis system(100) includes a sealing fluid delivery system that includes a sharedsealing fluid inlet (420).

In addition to those components, the fluid analysis system (100) mayinclude additional components. For example, the fluid analysis system(100) may include inlets (522-1, 522-2) through which fluid isintroduced. Specifically, a sealing fluid may be introduced into thefluid analysis system (100) via a sealing fluid inlet (522-1).Similarly, a fluid sample may be introduced into the fluid analysissystem (100) via a sample inlet (522-2). The fluid analysis system (100)may also include a number of actuators (524) to transport the sealingfluid and the fluid sample throughout the fluid analysis system (100).Specifically, sealing fluid actuators (524-2) may be drive the sealingfluid towards the respective fluid branches (104-1, 104-2). Forsimplicity, a single instance of a sealing fluid actuator (524-2) isindicated with a reference number. Similarly, the fluid analysis system(100) may include sample actuators (524-1) to drive the fluid sampletowards the analysis chamber (416). For simplicity, a single instance ofa sample actuator (524-1) is indicated with a reference number.

The fluid analysis system (100) may also include outlets (526). That is,after an operation occurs, the fluid sample may be passed, via an outletchannel (414) to a number of outlets (526) which may be ejectingactuators, such as inkjet nozzles, that eject the fluid sample onto asurface.

FIG. 6 is a diagram of a fluid analysis system (100) with a fluid seal,according to an example of the principles described herein. The exampledepicted in FIG. 6 allows for the asymmetric sealing of the inletchannel (102) and the outlet channel (414) of the analysis chamber(416). That is, it may be desirable to seal the inlet channel (102)either before or after sealing the outlet channel (414). This may beaccomplished in a number of ways. As described above in FIGS. 4A and 4B,this may be accomplished via a sequential activation of differentheaters (FIG. 1, 110 ). For example, different heaters (FIG. 1, 110-1,110-2 ) associated with the different gas chambers (106) may beactivated at different times as described above in connection with FIGS.4A and 4B.

In another example, the first fluid branch (104-1) may have a differentlength than the second fluid branch (104-2). The longer the branch, thegreater temperature increase and duration are exhibited in driving thesealing fluid from the sealing fluid inlet (420) to fill the branch.Accordingly, in the example depicted in FIG. 6 , the gas in the firstgas chamber (106-1) would fill the shorter first fluid branch (104-1)earlier than the gas in the second gas chamber (106-2) would fill thelonger second fluid branch (104-2). Accordingly, a sequenced closing ofthe inlet channel (102) and outlet channel (414) is provided.

In another example, the sequential closing of the inlet channel (102)and the outlet channel (414) may be provided by having a first gaschamber (106-1) that has a different size than the second gas chamber(106-2). That is, like the different length fluid branches (104),different size gas chambers (106) provide different volumes into whichthe trapped gas may expand. Accordingly, in the example depicted In FIG.6 , the gas in the first chamber (106-1) would expand into the firstfluid branch (104-1) earlier than the gas in the second gas chamber(106-2) would expand into the second fluid branch (104-2).

Moreover, as depicted in FIG. 6 , the fluid analysis system (100) mayhave an asymmetric arrangement of components. For example, rather thanplacing the analysis chamber (416) between the gas chambers (106), bothgas chambers (106) may be disposed on a single side of the analysischamber (416). Doing so may facilitate other components of the fluidanalysis system (100) or the larger system of which the fluid analysissystem (100) is a component.

In summary, such a fluid analysis system 1) provides an evaporation freeenvironment in which any number of biological or chemical reactions maytake place, 2) provides a seal using immiscible fluid which does notevaporate and does not interfere with the biological or chemicalreactions; and 3) does not include moveable parts which are susceptibleto mechanical breakdown. However, the devices disclosed herein mayaddress other matters and deficiencies in a number of technical areas.

1. A fluid analysis system, comprising: an inlet channel to an analysischamber, wherein the analysis chamber is to receive a fluid sample to beanalyzed; a fluid branch having a fluidic junction along the inletchannel; a gas chamber to house a volume of trapped gas, the gas chamberbeing in fluid communication with the fluid branch; a sealing fluiddelivery system to fill the fluid branch with a sealing fluid; and aheater adjacent the gas chamber to heat the gas chamber such that thetrapped gas expands to push the sealing fluid into the inlet channel toseal the analysis chamber.
 2. The fluid analysis system of claim 1,further comprising a first capillary break at the fluidic junction toprevent the sealing fluid from entering the inlet channel prior toheating the gas chamber.
 3. The fluid analysis system of claim 2,further comprising a second capillary break in the fluid branch upstreamof the gas chamber to prevent backflow of the sealing fluid through thefluid branch.
 4. The fluid analysis system of claim 3, wherein thesecond capillary break has a smaller opening than the first capillarybreak.
 5. The fluid analysis system of claim 3, wherein the secondcapillary break has different characteristics as compared to the firstcapillary break.
 6. The fluid analysis system of claim 5, wherein acharacteristic that is different between the second capillary break andthe first capillary break is selected from the group consisting of: alength; a width; a capillary break gap; a holding pressure; and ahydrophobicity.
 7. The fluid analysis system of claim 1, furthercomprising a gas chamber capillary break to prevent the sealing fluidfrom entering the gas chamber.
 8. The fluid analysis system of claim 1,wherein the sealing fluid has a lower vapor pressure than the fluidsample and is immiscible with the fluid sample.
 9. The fluid analysissystem of claim 1, further comprising a number of actuators to transportthe sealing fluid and the fluid sample throughout the fluid analysissystem.
 10. A method, comprising: introducing a sealing fluid through afluid branch to a fluidic junction with an inlet channel of an analysischamber; introducing a fluid sample into the analysis chamber via theinlet channel; heating trapped gas in a gas chamber that is in fluidcommunication with the fluid branch; and via expansion of the trappedgas in the gas chamber, transporting the sealing fluid into a body ofthe inlet channel to seal the analysis chamber and prevent evaporationfrom the analysis chamber.
 11. The method of claim 10, wherein thesealing fluid is selected from the group consisting of: silicon oil;mineral oil; hexadecane; a hydrofluoroether-based fluid; and afluorocarbon-based fluid.
 12. The method of claim 10, further comprisingpreventing: the sealing fluid from entering the body of the inletchannel until the gas chamber is heated; flow of the sealing fluid intothe gas chamber; and backflow of the sealing fluid through the fluidbranch.
 13. A fluid analysis system, comprising: an analysis chamberhaving an inlet channel and an outlet channel; a first fluid branchhaving a fluidic junction along the inlet channel; a second fluid branchhaving a fluidic junction along the outlet channel; a first gas chamberin fluid communication with the first fluid branch; a second gas chamberin fluid communication with the second fluid branch; a sealing fluiddelivery system to fill the first fluid branch and second fluid branchwith a sealing fluid; and a heating system to heat the first gas chamberand the second gas chamber such that trapped gas expands to push thesealing fluid into the inlet channel and outlet channel.
 14. The fluidanalysis system of claim 13, wherein the first gas chamber and firstfluid branch have different properties than the second gas chamber andsecond fluid branch, respectively.
 15. The fluid analysis system ofclaim 13, wherein the sealing fluid delivery system comprises a sharedsealing reservoir between the first fluid branch and the second fluidbranch.